Search Results (262)

Background: Artificial non-nutritive sweeteners (NNSs), such as sucralose, have been associated with gut microbiota (GM) alterations. However, the impact of rebaudioside A (reb A), a natural NNS, on GM has received limited scrutiny. Objective: The objective of this study was to examine the response of GM composition to sucralose and reb A in rats under two dietary conditions. Methods: Male Wistar rats (150–200 g) fed with a normal diet (ND) or a high-fat diet (HFD) were randomly assigned to receive sucralose (SCL), reb A (REB), glucose (GLU, control), or sucrose (SUC). The NNS interventions were administered in water at doses equivalent to the acceptable daily intake (ADI). After eight weeks, the GM composition in fecal samples was analyzed through 16S ribosomal RNA gene sequencing. Results: The NNSs did not modify the diversity, structure, phylum-level composition, or Firmicutes/Bacteroidetes (F/B) ratio of the GM in rats under ND or HFD. However, REB with HFD decreased Bacilli and increased Faecalibacterium abundance at the class level. SCL and REB in rats receiving ND reduced the genera Romboutsia and Lactobacillus. Conclusions: Our study suggests that when sucralose or reb A is consumed at recommended doses, there is no alteration in the diversity or the composition of the GM at the phylum level. The clinical relevance of these findings lies in the potential modifications of the GM at specific taxonomic levels by the consumption of these NNSs. Further research involving humans and including a broader range of microbial analyses is warranted. Full article

The gut–brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management. Full article

The human exposome, including dietary exposures such as pesticides, additives, and environmental contaminants, plays a critical role in shaping the gut microbiota (GM) and long-term health outcomes. While the Mediterranean Diet is known for its health-promoting effects, the role of food quality, specifically organic vs. conventional products, in modulating GM within this dietary pattern remains underexplored. The aim of this study was to evaluate (1) whether an Italian Mediterranean Organic Diet (IMOD) confers additional benefits compared to an Italian Mediterranean non-Organic Diet (IMnOD), and (2) the impact of IMOD and IMnOD versus a free diet (No Diet) on GM and anthropometric parameters. A randomized, controlled trial was conducted on 39 healthy subjects. Eligible subjects were divided into the following groups: (1) 4 weeks No Diet, (2) 4 weeks IMOD, and (3) 4 weeks IMnOD. Microbiota profiling (16S rRNA sequencing), body composition (BIA), and dietary adherence (MEDAS, FFQ) were evaluated. Distinct microbial shifts following both IMOD and IMnOD compared to No Diet were revealed. Several taxa previously associated with short-chain fatty acid (SCFA) biosynthesis (i.e., Anaerobutyricum hallii, Anaerostipes hadrus, and Dorea longicatena) were increased after both Mediterranean Diet interventions, while Parabacteroides distasonis showed a specific increase in the IMOD group. No significant changes in body weight or composition were observed. These findings suggest that adherence to a Mediterranean Diet, regardless of food source, reshapes the gut microbiota, while organic food intake may influence specific microbial trajectories. Our results support the relevance of food quality in dietary interventions. Full article

Bipolar disorder (BD) is a multifactorial mental disease with a prevalence of 1–5% in adults, caused by complex interactions between genetic and environmental factors. Environmental factors contribute to gene expression alterations through epigenetic mechanisms without changing the underlying DNA sequences. Interactions between the gut microbiota (GM) and diverse external factors, such as nutritional composition, may induce epigenetic alterations and increase susceptibility to BD. While epigenetic mechanisms are involved in both the pathogenesis of BD and drug treatment responses, epigenetic marks could be employed as predictors and indicators of drug response. This review highlights recent studies on the potential role of epigenetic aberrations in the development and progression of BD. Next, we focus on drug response-related alterations in the epigenetic landscape, including DNA methylation, histone modifications, and non-coding RNAs. Afterward, we delve into the potential roles of GM-induced epigenetic changes in the pathogenesis of BD and GM-based therapeutic strategies aimed at improving BD outcomes through epigenetic modifications. We also discuss how BD drugs may exert beneficial effects through modulation of the GM and the epigenome. Finally, we consider future research strategies that could address existing challenges. Full article

Background/Objectives: The gut microbiota (GM) is pivotal for immune regulation, metabolism, and neurodevelopment. Infants undergoing surgery for congenital gastrointestinal anomalies are especially prone to microbial imbalances, with a paucity of beneficial bacteria (e.g., Bifidobacteria and Bacteroides) and diminished short-chain fatty acid production. Dysbiosis has been associated with severe complications, including necrotizing enterocolitis, sepsis, and feeding intolerance. This narrative review aims to critically examine strategies for microbiota modulation in this high-risk cohort. Methods: An extensive literature analysis was performed to compare the evolution of GM in healthy neonates versus those requiring gastrointestinal surgery, synthetizing strategies to maintain eubiosis, such as early nutritional interventions—particularly the use of human milk—along with antibiotic management and supplementary treatments including probiotics, prebiotics, postbiotics, and lactoferrin. Emerging techniques in metagenomic and metabolomic analysis were also evaluated for their potential to elucidate microbial dynamics in these patients. Results: Neonates undergoing gastrointestinal surgery exhibit significant alterations in microbial communities, characterized by reduced levels of eubiotic bacteria and an overrepresentation of opportunistic pathogens. Early initiation of enteral feeding with human milk and careful antibiotic stewardship are linked to improved microbial balance. Adjunctive therapies, such as the administration of probiotics and lactoferrin, show potential in enhancing gut barrier function and immune modulation, although confirmation through larger-scale studies remains necessary. Conclusions: Modulating the GM emerges as a promising strategy to ameliorate outcome in neonates with congenital gastrointestinal surgical conditions. Future research should focus on the development of standardized therapeutic protocols and the execution of rigorous multicenter trials to validate the efficacy and safety of these interventions. Full article

Neuroinflammation is a hallmark of many neuropsychiatric disorders (NPD), which are among the leading causes of disability worldwide. Emerging evidence highlights the significant role of the gut microbiota (GM)–immune system–brain axis in neuroinflammation and the pathogenesis of NPD, primarily through epigenetic mechanisms. Gut microbes and their metabolites influence immune cell activity and brain function, thereby contributing to neuroinflammation and the development and progression of NPD. The enteric nervous system, the autonomic nervous system, neuroendocrine signaling, and the immune system all participate in bidirectional communication between the gut and the brain. Importantly, the interaction of each of these systems with the GM influences epigenetic pathways. Here, we first explore the intricate relationship among intestinal microbes, microbial metabolites, and immune cell activity, with a focus on epigenetic mechanisms involved in NPD pathogenesis. Next, we provide background information on the association between inflammation and epigenetic aberrations in the context of NPD. Additionally, we review emerging therapeutic strategies—such as prebiotics, probiotics, methyl-rich diets, ketogenic diet, and medications—that may modulate the GM–immune system–brain axis via epigenetic regulation for the prevention or treatment of NPD. Finally, we discuss the challenges and future directions in investigating the critical role of this axis in mental health. Full article

The increasing prevalence of non-communicable diseases (NCDs) is strongly associated with gut microbiota (GM) imbalances and reduced short-chain fatty acid (SCFA) production, primarily driven by poor diet and microbial dysbiosis. Since SCFAs are crucial for gut health, immune regulation, and inflammation control, restoring their levels is a key therapeutic target. SCFA-acylated naringin derivatives offer a novel approach by enhancing SCFA delivery and modulating GM composition. In this study, we investigated the effects of naringin acetate and naringin propionate on SCFA production using a 24 h short-term in vitro batch fecal fermentation model with microbiota from two donors. Naringin propionate and naringin plus free propionate significantly increased propionate levels by 0.74 mM and 0.75 mM, respectively (p < 0.0001), while naringin acetate induced a smaller increase of 0.26 mM. Donor-specific reflected differences in microbial communities, yet SCFA enhancement was observed across samples. Additionally, naringin treatments stimulated the growth of beneficial polyphenol-metabolizing bacteria, including Bacteroides, Streptococcus, and Eubacterium siraeum. The strong effect of naringin propionate suggests a sustained SCFA release mediated by microbial enzymes. These preliminary results highlight the potential of SCFA-acylated flavonoids as functional dietary components to increase SCFA bioavailability and support gut health, particularly from citrus-derived co-products. Full article

Lifestyle, diet, and genetics are established risk factors for developing colorectal cancer (CRC). In recent years, the role of the gut microbiota (GM) has been increasingly highlighted in several studies, suggesting an effect on both the disease’s pathogenesis and the efficacy and tolerability of treatments. We conducted a search on Medline, aiming to identify published studies exploring the role of the GM in the development and treatment of CRC. Dysbiosis, an imbalance in GM, is common in CRC patients and is associated with precancerous lesions, aggressive tumors, and varied therapy outcomes. Restoring GM balance can reduce treatment complications and may improve prognosis. The review details how GM influences CRC through metabolite production, inflammation modulation, and immune response alteration. Diet significantly impacts GM composition, with processed meats and high-fat diets increasing CRC risk, while fiber-rich diets are protective. The role of the GM in CRC treatments like surgery, chemotherapy, radiotherapy, and immunotherapy is also explored, noting its influence on complications, chemoresistance, and treatment efficacy. Future strategies involving GM modulation through diet, probiotics, and fecal microbiota transplantation (FMT) show promise for CRC prevention and treatment, warranting further research. Full article

The extensive research and studies conducted over the past decade have greatly improved our comprehension of the pathogenesis and risk factors associated with Spondyloarthritis (SpA). In addition, they have contributed to the advancement of novel therapeutic approaches. Although genetics still represents the primary risk factor for SpA, increasing evidence presented in this review suggests that environmental factors—such as air pollution, smoking, gut microbiota (GM), infections, and diet—also contribute to its pathogenesis. In detail, environmental particulate matters (PMs), which include ligands for the aryl hydrocarbon receptor—a cytosolic transcription factor responsive to toxic substances—facilitate the differentiation of T Helper 17 (Th17) cells, potentially exacerbating the autoinflammatory processes associated with SpA. Furthermore, smoking influences both the cellular and humoral aspects of the immune response, resulting in leukocytosis, impaired leukocyte functionality, and a decrease in various cytokines and soluble receptors, including interleukin (IL) 15, IL-1 receptor antagonist (IL-1Ra), IL-6, soluble IL-6 receptor (sIL-6R), as well as the vascular endothelial growth factor (VEGF) receptor. Studies have indicated that patients with SpA exhibit an increased prevalence of antibodies directed against a conserved epitope shared by the human leukocyte antigen B27 (HLA-B27)- and Klebsiella nitrogenase, in comparison to HLA-B27-positive controls. Additionally, current evidence regarding the GM suggests the presence of a gut–joint–skin axis, wherein the disruption of the mucosal barrier by specific bacterial species may enhance permeability to the gut-associated lymphoid tissue (GALT), resulting in localized inflammation mediated by Th1 and Th17 cells, as well as IL-17A. Finally, this review discusses the role of diet in shaping the microbial composition and its contribution to the pathogenesis of SpA. A comprehensive understanding of the mechanisms by which environmental factors influence the pathogenesis and progression of the disease could facilitate the development of novel personalized therapies targeting both external and internal environmental exposures, such as the gut microbial ecosystem. Full article

Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety. Full article

Background: Phenolic compounds, particularly anthocyanins and proanthocyanidins (PACs), are poorly absorbed in the upper digestive tract and reach the colon largely intact, where they may influence gut microbiota (GM) composition and, in turn, impact host health. We hypothesized that a PAC-rich aronia extract would beneficially modulate the GM, promote the growth of health-associated bacteria, and enhance short-chain fatty acid (SCFA) production across different colon sections, with partial reversion effects after supplementation ends. Methods: The Twin-M-SHIME^® system was used to simulate the digestion and colonic fermentation in two donors with contrasting microbiota profiles. The experimental design included four phases: stabilization (14 days), control (7 days), treatment with 500 mg/day PAC-rich aronia extract (21 days), and wash-out (10 days). SCFA production was monitored, and changes in microbiome composition were assessed using 16S rRNA gene sequencing. Results: PAC-rich aronia extract significantly modulated SCFA levels, increasing butyrate and reducing acetate, with some inter-donor variability. SCFA concentrations tended to return to baseline after the wash-out (WO) period. Metagenomic analysis revealed a decrease in Collinsella, Sutterella, Selenomonas, and Parabacteroides—genera linked to low-fiber diets and gut inflammation—while promoting Proteobacteria (e.g., Escherichia-Shigella, Klebsiella) and butyrate-associated Firmicutes such as Lactiplantibacillus. Although some microbial shifts partially reverted during the wash-out (e.g., Akkermansia, Bacteroides, and Bifidobacterium), other changes persisted. Conclusions: These findings suggest that PAC-rich aronia extract beneficially modulates GM and SCFA production, but continuous intake may be necessary to maintain these effects over time. Full article

The gut microbiota (GM) may play a crucial role in the development and progression of central nervous system (CNS) diseases. Microecologics and exercise can influence the composition and function of GM, thereby exerting positive effects on the CNS. Combined interventions of exercise and microecologics are expected to more comprehensively and effectively address CNS diseases through the microbiota–gut–brain axis (MGBA), potentially outperforming single interventions. However, there is currently a lack of relevant reviews on this topic. In this review, we examine the associations between changes in the microbiota and CNS diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). We also summarize studies on various types of microecologics (such as probiotics, prebiotics, synbiotics, and postbiotics) and exercise in improving CNS disease symptoms. Although current individual studies on microecologics and exercise have achieved certain results, the mechanisms underlying their synergistic effects remain unclear. This review aims to explore the theoretical basis, potential mechanisms, and clinical application prospects of combined interventions of microecologics and exercise in improving CNS diseases through the MGBA, providing a scientific basis for the development of more comprehensive and effective therapeutic interventions. Full article

Precision nutrition-targeted gut microbiota (GM) may have therapeutic potential not only for age-related diseases but also for slowing the aging process and promoting longer healthspan. Recent studies have shown that restoring a healthy symbiosis of GM by counteracting dysbiosis (DYS) through precise nutritional intervention is becoming a major target for extending healthspan. Microbiota-accessible borate (MAB) complexes, such as boron (B)–pectins (rhamnogalacturonan–borate) and borate–phenolic esters (diester chlorogenoborate), have a significant impact on healthy host–microbiota symbiosis (HMS). The mechanism of action of MABs involves the biosynthesis of the autoinducer-2–borate (AI-2B) signaling molecule, B fortification of the mucus gel layer by the MABs diet, inhibition of pathogenic microbes, and reversal of GM DYS, strengthening the gut barrier structure, enhancing immunity, and promoting overall host health. In fact, the lack of MAB complexes in the human diet causes reduced levels of AI-2B in GM, inhibiting the Firmicutes phylum (the main butyrate-producing bacteria), with important effects on healthy HMS. It can now be argued that there is a relationship between MAB-rich intake, healthy HMS, host metabolic health, and longevity. This could influence the deployment of natural prebiotic B-based nutraceuticals targeting the colon in the future. Our review is based on the discovery that MAB diet is absolutely necessary for healthy HMS in humans, by reversing DYS and restoring eubiosis for longer healthspan. Full article

Background/Objectives: Sarcopenia (SA), an age-related impairment in skeletal muscle mass and function, is related to gut microbiota (GM) through inflammation and short-chain fatty acid (SCFA) generation. However, data on this relationship in older Japanese adults remain limited. We investigated the relationship of GM composition with SA, based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, among elderly Japanese outpatients. Methods: Between June 2022 and January 2023, this prospective cross-sectional study enrolled 356 community-dwelling outpatients aged ≥ 65 years at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center. SA was determined based on the AWGS 2019 consensus criteria. GM was analyzed using 16S rRNA gene sequencing, and alpha/beta diversity, taxonomic composition, detection rates, and correlations with skeletal muscle mass index (SMI), grip strength, and gait speed were investigated. Results: Among 356 (144 males, 212 females) participants, 50 (35 males, 15 females) had SA. Differences in GM diversity and composition were primarily noted among male participants. Men with SA had lower alpha diversity and distinct beta diversity profiles. Six bacterial genera—Eubacterium I, Fusicatenibacter, Holdemanella, Unclassified Lachnospira, Enterococcus H, and Bariatricus—had lower abundances in the SA group. Several of these genera showed positive correlations with SMI, grip strength, and gait speed. Conversely, no differences in GM characteristics were seen among females. Conclusions: GM composition was associated with SA among older Japanese men. These sex-specific differences emerged consistently, highlighting the potential of microbiota-based strategies for SA prevention in older males. Full article

Background: The disruption of the intestinal barrier and the imbalance of the gut microbiota (GM) seem to play a major role in the complex pathogenesis of irritable bowel syndrome (IBS). Specific microbial strains could improve the gut microenvironment, promoting anti-inflammatory pathways; similarly, vitamin D supplementation could play a role in enhancing the barrier integrity and modulating the immune response in the gut. This study aims to evaluate the efficacy of a new multistrain probiotic, combined with vitamin D, in improving gut barrier function in IBS without constipation. Methods: In this phase IIb double-blind randomized placebo-controlled, parallel-group, multicenter, clinical trial, 35 patients were treated for 12 weeks with OttaBac^®, a high concentration multistrain probiotic plus cholecalciferol, or placebo and were followed up until week 16. Symptoms, quality of life, intestinal permeability, fecal biomarkers, and microbiota composition were evaluated at 0, 12, and 16 weeks. Results: Mean zonulin values showed a significant progressive reduction in the active group (−10.2 ng/mL at week 12, p = 0.0375; −19.5 ng/mL at week 16, p = 0.0002), with a significant difference between groups at week 16 in the per-protocol population (−19.01, p = 0.0053). The active group showed a more stable trend toward improvement in stool frequency and consistency at both week 12 and 16, with a significant improvement compared to the baseline and to the placebo group (−23.2, p = 0.0265, and 5.57 vs. −23.2, p = 0.0492, respectively). No differences were found in regards to the lactulose/mannitol ratio, Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) and Short Form Health Survey (SF-36) total scores, plasmalemmal vesicle associated protein-1 (PV-1), and citrulline levels. In the active group, Bifidobacterium animalis subsp. lactis and Streptococcus thermophilus levels were increased (p < 0.05), while those for Lachnospira were decreased (p < 0.05), and significant changes in Actinobacteria and Proteobacteria were observed (p < 0.05). Lactate (p < 0.01) and acetate (p < 0.05) levels increased post-treatment. Correlation analysis pointed out a significant association between the microbial biomarkers and the symptoms (p < 0.05). Conclusions: Probiotic plus vitamin D could improve IBS-associated symptoms through gut microbiota modulation and gut barrier enhancement, with persistent benefits after treatment discontinuation. Full article